Is B3GLCT p.Pro112Leu (c.335C>T) pathogenic?

B3GLCT p.Pro112Leu (c.335C>T) is classified Uncertain significance in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). AlphaMissense: likely benign (0.3131); Ultra-rare (popmax 0.0165%, mid); Associated with Peters plus syndrome.

What condition is associated with B3GLCT p.Pro112Leu (c.335C>T)?

B3GLCT p.Pro112Leu (c.335C>T) is associated with Peters plus syndrome (ClinVar).

How common is B3GLCT p.Pro112Leu (c.335C>T) in the general population?

B3GLCT p.Pro112Leu (c.335C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about B3GLCT p.Pro112Leu (c.335C>T)?

AlphaMissense predicts likely benign (score 0.3131) — an in-silico prediction, not a clinical call.

B3GLCT p.Pro112Leu

c.335C>T · rs372324692 · VCV1371999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peters plus syndrome

Computational evidence

Protein change
AlphaMissense	0.3131	likely benign
REVEL	0.657	pathogenic-leaning
SaProt	LLR -13.68	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.20	donor loss · deltas
Pangolin	Δ0.21	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 130 kb · p 0.26 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00403% 65/1,612,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
South Asian	0.00549%	18,205
European (non-Finnish)	0.00475%	21,057
East Asian	0.00223%	44,864
Remaining individualsnot grpmax-eligible	0.0016%	62,460
African / African-American	0.00134%	74,900

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: B3GLCT
Protein: p.Pro112Leu
Coding: c.335C>T
MANE Select: NM_194318
dbSNP: rs372324692
Type: single nucleotide variant
Location: chr13:31247087 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB

Full B3GLCT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Peters plus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B3GLCT p.Pro112= Likely benign ★ same residue
B3GLCT c.459+1G>A Pathogenic/Likely pathogenic ★★ same condition
B3GLCT c.660+1G>A Pathogenic ★★ same condition
B3GLCT p.Tyr380Ter Pathogenic/Likely pathogenic ★★ same condition
B3GLCT c.*1752C>T Uncertain significance ★★ same condition
B3GLCT p.Arg377His Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asn243Ser Uncertain significance ★★ ⚠ same condition
B3GLCT p.Asp469Asn Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/b3glct-p-pro112leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown